(Philadelphia, PA) - Patients with multiple myeloma
suffer from a malignant proliferation of plasma cells in their bone
marrow. The standard treatment for this form of cancer is high-dose
chemotherapy and transplantation of one's own blood-producing adult
stem cells; however, this aggressive treatment wipes out the mature
immune-system cells of patients - leaving them vulnerable to infection.
A complementary treatment currently approved is to vaccinate myeloma
patients against pneumococcus, a common bacterial infection, a year
after their transplantation. But why wait a year, wondered researchers
at the University of Pennsylvania School of Medicine?
Their own investigation revealed that protective levels of immunity
against pneumococcus could be obtained in patients who were given
the prophylactic bacterial vaccine in addition to a new autologous
T-cell-based vaccine only two weeks after transplantation. Indeed,
protection developed in the patients within a month after the transplantation.
Their clinical trial is described in this week's online edition
of Nature Medicine.
“We found that we can rapidly rebuild the patients' immunity
after chemotherapy and stem-cell transplant,” said Carl
June, MD, Director of Translational Research at Penn's
Abramson Cancer Center. “For future studies,
we will apply the principles learned from this study to hone the
development of a cancer vaccine aimed directly at tumors and other
cancers,” added June, who is also Professor of Pathology and
Laboratory Medicine in Penn's School of Medicine.
Early Measures Prove Highly Effective
Patients in the study were all given two pneumococcal vaccines one
month and three months after their stem-cell transplants; whereas
normally they would have to wait up to a year. The patients were
then divided into four groups: one group received an initial pneumococcal
vaccine before transplantation and chemotherapy, then a T-cell vaccine
immediately after; a second group received the pneumococcal vaccine
before transplantation and chemotherapy, but received the T-cell
vaccine three months after their transplant and chemotherapy. The
last pair of groups did not get the initial pneumococcal vaccine
before the standard transplant and chemotherapy, but did receive
the T-cell vaccine immediately after or three months after the standard
The researchers found that the patients in the group that received
the early pneumococcal vaccine plus the early T-cell vaccine infusion
had an immune response that was protective and higher than often
achieved in normal patients who do not have cancer.
Custom-Designed T-Cell Therapies Will Enhance Immunity
At the recently opened Clinical Cell and Vaccine Production Facility
at Penn, “we have been using new cell-based custom therapeutics
derived from a patient's own T cells in this and other studies,
with the long term goal of improving outcome and extending life,”
explains co-author Bruce Levine, PhD, who directs
the Facility. T-cells are taken from a patient and expanded about
a thousand fold. The engineered T-cells are then given back to the
patient a few weeks later via an infusion. The newly grown T cells
continue to grow in the patient, which is different than a red blood
cell transfusion. The effect of this therapy is to quickly repopulate
a patient's immune system with mature cells that can support immunity
against infections, and potentially against tumors.
“This study showed how to take a vaccine that is a failure
in people after chemotherapy and to modify it so that it works in
cancer patients after chemotherapy,” says June. “The
surprising thing is that the vaccine works better than normal in
many of the patients. This is the first step in developing a new
form of personalized therapy for the treatment of cancer, where
engineered T-cells will be used to boost the immune system, essentially
priming it to make cancer vaccines work better.”
In addition to June and Levine, study co-authors include Edward
Stadtmauer from Penn and Aaron Rapoport and Alan Cross, University
This study was funded by the Leukemia and Lymphoma Society, the
National Institute of Allergy and Infectious Diseases, the National
Cancer Institute, and the Multiple Myeloma Research Foundation.
PENN Medicine is a $2.7 billion enterprise
dedicated to the related missions of medical education, biomedical
research, and high-quality patient care. PENN Medicine consists
of the University of Pennsylvania School of Medicine (founded in
1765 as the nation's first medical school) and the University of
Pennsylvania Health System.
Penn’s School of Medicine is ranked #2 in the nation
for receipt of NIH research funds; and ranked #4 in the nation in
U.S. News & World Report’s most recent ranking of top
research-oriented medical schools. Supporting 1,400 fulltime faculty
and 700 students, the School of Medicine is recognized worldwide
for its superior education and training of the next generation of
physician-scientists and leaders of academic medicine.
The University of Pennsylvania Health System comprises: its
flagship hospital, the Hospital of the University of Pennsylvania,
consistently rated one of the nation’s “Honor Roll”
hospitals by U.S. News & World Report; Pennsylvania Hospital,
the nation's first hospital; Penn Presbyterian Medical Center; a
faculty practice plan; a primary-care provider network; two multispecialty
satellite facilities; and home health care and hospice.
The Abramson Cancer Center of the University of Pennsylvania
was established in 1973 as a center of excellence in cancer
research, patient care, education and outreach. Today, the Abramson
Cancer Center ranks as one of the nation’s best in cancer
care, according to U.S. News & World Report, and is one of the
top five in National Cancer Institute (NCI) funding. It is one of
only 39 NCI-designated comprehensive cancer centers in the United
States. Home to one of the largest clinical and research programs
in the world, the Abramson Cancer Center of the University of Pennsylvania
has 275 active cancer researchers and 250 Penn physicians involved
in cancer prevention, diagnosis and treatment.